RT Journal Article
T1 Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.
A1 Posset, Roland
A1 Garcia-Cazorla, Angeles
A1 Valayannopoulos, Vassili
A1 Leao-Teles, Elisa
A1 Dionisi-Vici, Carlo
A1 Brassier, Anaïs
A1 Burlina, Alberto B
A1 Burgard, Peter
A1 Cortes-Saladelafont, Elisenda
A1 Dobbelaere, Dries
A1 Couce, Maria L
A1 Sykut-Cegielska, Jolanta
A1 Haberle, Johannes
A1 Lund, Allan M
A1 Chakrapani, Anupam
A1 Schiff, Manuel
A1 Walter, John H
A1 Zeman, Jiri
A1 Vara, Roshni
A1 Kölker, Stefan
K1 Argininosuccinate Synthase
K1 Neonatal Screening
K1 Patient Acuity
K1 Emergency Service, Hospital
K1 Lyases
AB Background: Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation. Aims: Determining the effect of diagnostic and therapeutic interventions on the neurological outcome. Methods: Evaluation of baseline, regular follow-up, and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry. Results: About two-thirds of UCD patients remained asymptomatic until age 12 days (i.e., the median age at diagnosis of patients identified by newborn screening (NBS)), suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 μmol/L), best predicted the neurological outcome. Conclusions: Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimized long-term and emergency treatment.
PB Wiley
YR 2016
FD 2016-04-22
LK http://hdl.handle.net/10668/12009
UL http://hdl.handle.net/10668/12009
LA en
NO Posset R, Garcia-Cazorla A, Valayannopoulos V, Teles EL, Dionisi-Vici C, Brassier A, et al. Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders. J Inherit Metab Dis. 2016 Sep;39(5):661-672
DS RISalud
RD Apr 5, 2025